CN104721223B - A kind of injection pharmaceutical composition of compound electrolyte and preparation method thereof - Google Patents
A kind of injection pharmaceutical composition of compound electrolyte and preparation method thereof Download PDFInfo
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- CN104721223B CN104721223B CN201510086897.9A CN201510086897A CN104721223B CN 104721223 B CN104721223 B CN 104721223B CN 201510086897 A CN201510086897 A CN 201510086897A CN 104721223 B CN104721223 B CN 104721223B
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Abstract
The present invention relates to injection pharmaceutical compositions of a kind of compound electrolyte and preparation method thereof, every 1000ml contains 5.26g sodium chloride, 0.37g potassium chloride, 0.30g magnesium chloride, the Multiple electrolytes injection pharmaceutical composition of 5.02g sodium gluconate and 3.68g sodium acetate, preparation method are as follows: be added at one time whole water for injection, it is placed in Agitation Tank, sodium gluconate is put by recipe quantity, sodium acetate, sodium chloride, potassium chloride and magnesium chloride, stirring and dissolving, make solution ph to 6.0~8.0 with or without the use of pH adjusting agent adjusting, then 0.01%g/ml~0.05%g/ml active carbon stirring and adsorbing is added, successively with 0.45 μm, 0.22 μm of filtering with microporous membrane, it is filling, 121 DEG C of pressure sterilizings.The product of the method preparation, electrolyte ingredient reach unanimity with vivo environment to the maximum extent, can play the effect for maintaining vivo environment balance to greatest extent, validity and safety are higher, while operating very simple, time and labour saving, energy saving.
Description
Technical field
The present invention relates to pharmaceutical compositions, more particularly, to a kind of preparation method of Multiple electrolytes injection, and
The Multiple electrolytes injection composition prepared by this method.
Background technique
Multiple electrolytes injection is a kind of effective circulating blood volume supplied by parenteral liquid to maintain body, is guaranteed each
The oxygen of organ and tissue supplies, while maintaining the drug of body water, electrolyte and acid-base balance, during being clinically usually used in operation
Maintain patient with operation vital signs stable.Every 1000ml contain 5.26g sodium chloride, 0.37g potassium chloride, 0.30g magnesium chloride,
The Multiple electrolytes injection of 5.02g sodium gluconate and 3.68g sodium acetate, with Lactated Ringer'S Solution or compound NaCl etc.
Injection is compared, and the content of electrolyte, pH value, osmotic pressure are more consistent with blood plasma, and since it carries soda acid buffering
System, therefore the influence in use to human body acid-base and electrolyte is smaller, it is easier to body environment balance is effectively maintained,
Therefore also it is more in line with the medication requirement of clinician.
For injection, bacterial endotoxin or pyrogen are highly important quality index, because containing excess bacteria endogenous toxic material
Be likely to occur after element or the injection of pyrogen injection human body feel cold, generate heat, the adverse reactions such as Nausea and vomiting, serious person's even dusk
Fan, collapse, such as rescue not in time, can threat to life, therefore in critical field be very by bacterial endotoxin or pyrogen control
It is necessary.In injection production process, activated carbon adsorption is the method for maximally efficient removal bacterial endotoxin or pyrogen,
But charcoal adsorption process is non-selective adsorption, and while adsorbing bacterial endotoxin or pyrogen, often adsorbing drug has
Ingredient is imitated, active ingredient loss is ultimately caused.
Every 1000ml recipe quantity be 5.26g sodium chloride, 0.37g potassium chloride, 0.30g magnesium chloride, 5.02g sodium gluconate and
The Multiple electrolytes injection of 3.68g sodium acetate, using prior art preparation, total chlorine amount be usually 0.31%g/ml~
0.33%g/ml, compared with total chlorine amount 0.358%g/ml practical in prescription, the up to Cl of 7.8%g/ml~13.4%g/ml-
It loses during the preparation process, i.e. Cl-Content be only labelled amount 86.5%g/ml~92.1%g/ml, this and U.S.'s medicine
In the various Multiple electrolytes injection quality standards of allusion quotation, it is desirable that the content of each ingredient of electrolyte is the 90%~110% of labelled amount
Range is compared, and has very big gap, and is used for a long time and be will lead to blood chlorinity lower than human normal range (98mmol/L
~106mmol/L), due to Cl-It is only easy in renal tubule and Na+Successive re-absorbed anion, as Cl in crude urine-It reduces
When, renal tubule just reinforces H+、K+Discharge and Na+、HCO3-Reabsorption, and then cause hypochloraemia, cause in metabolic alkali
Poison.
On the other hand, active carbon is in absorption Cl-While, other ions can also be adsorbed, lead to Na+、K+、Mg2+Deng
The loss of important ion influences internal blood potassium, blood sodium and blood magnesium so that the difference of electrolyte injection and plasmatic environment expands
Concentration stablize, increase body intracellular metabolite burden, maintain vivo environment balance effect be also affected significantly, and by
In active carbon to Cl-、Na+、K+Adsorption capacity there is larger difference, lead to the loss amount of each ion component and non-uniform, because
This is also difficult to make up the electrolyte ingredient of loss in such a way that Excess quantities are with liquid.
CN101849961A discloses a kind of Multiple electrolytes injection and preparation method thereof: first by sodium gluconate and vinegar
Sour sodium is dissolved in the water for injection of total volume 80%, add sodium chloride, potassium chloride and magnesium chloride mix to completely it is molten
Solution, benefit inject water to recipe quantity, adjust pH to 4.0~8.0, heating medical fluid to 0.1%~0.5% needle of addition after 80 DEG C
With charcoal, after stirring and adsorbing 30min, refilter, refined filtration, sealing, sterilizing.Present invention applicant prepares injection according to the method described above
Liquid, detection find that its total chlorine amount is the g/ml of 0.312% g/ml~0.330%, and electrolyte ingredient the largest loss is up to 12.8% g/
Ml, and the above method needs for water for injection to be added in two portions, and bulk pharmaceutical chemicals dissolve in two times, production operation time-consuming work consuming, together
When also need injection being heated to certain temperature, generate a large amount of energy consumptions, these all will lead to the raising of production cost.
CN102935087B discloses a kind of preparation method of Multiple electrolytes injection: recipe quantity being added in dense preparing tank
50% water for injection, then sodium chloride, sodium gluconate, sodium acetate, potassium chloride and magnesium chloride are placed in Agitation Tank, it stirs molten
0.1%g/ml needle-use activated carbon is added in solution, and standing adsorption 15 minutes, filtration to dilute preparing tank, benefit injected water to nearly full dose,
PH to 7.5, secondary fine filtering, packing, sterilizing are adjusted after mixing evenly.Present invention applicant prepares injection according to the method described above,
Detection finds that its total chlorine amount is 0.320% g/ml, when still having the loss of 10.61% g/ml electrolyte ingredient, and using concentrated compounding method,
Drug concentration is higher, it is easier to cause process to be lost, and concentrated compounding method increases the complexity of technique, due to cumbersome, connect
Tentaculum tool is more, is easy to increase error and introduces the probability of impurity.
In view of the foregoing, developing one kind can ensure that existing Multiple electrolytes injection bacterial endotoxin meets rule
It is fixed, and can be by electrolyte losses, especially Cl-The damage control in low-level, thus electrolyte ingredient can to the maximum extent with body
Interior environment reaches unanimity, and can play the effect for maintaining vivo environment balance to the maximum extent, validity and safety are more similar
Product is higher, at the same operate very simple, time and labour saving, energy saving preparation method be very necessary.
Summary of the invention
The present invention need solve be to ensure that existing Multiple electrolytes injection under conditions of bacterial endotoxin is controllable,
During the preparation process, electrolyte ingredient, especially Cl-Greatly, product has certain security risks, and due to electrolysis for loss
Matter ingredient and internal plasmatic environment difference expand, and are unfavorable for maintaining homoiostasis, while existing preparation method is cumbersome
It is time-consuming, be easy to increase error and introduce the probability of impurity, the problems such as cost is excessively high.
In order to solve the above-mentioned technical problems, the present invention provides following technical schemes:
The present invention provides a kind of Multiple electrolytes injections, form as follows:
Above-mentioned injection the preparation method comprises the following steps: be added at one time whole water for injection, be placed in Agitation Tank, by recipe quantity
Sodium gluconate, sodium acetate, sodium chloride, potassium chloride and magnesium chloride are put into, stirring and dissolving is adjusted with or without the use of PH regulator
Make solution pH value to 6.0~8.0,0.01%g/ml~0.05%g/ml needle-use activated carbon stirring and adsorbing 15min is then added, successively
With 0.45 μm of miillpore filter, 0.22 μm of filtering with microporous membrane, filling, 121 DEG C of pressure sterilizing 12min~15min.
The preparation method without using the adjusting of PH regulator, it is preferable to use or make solution pH value to 6.5~7.5.
The preparation method, when adjusting solution pH value using PH regulator, the PH regulator is preferably hydrochloric acid or hydrogen
Sodium oxide molybdena.
The preparation method preferably adjusts solution pH value without using PH regulator.
Preferably, the sodium gluconate used, when being configured to 10mg/ml solution using water for injection, pH value
It is 6.3~7.2, and the sodium acetate used, when being configured to 30mg/ml solution using water for injection, pH value 8.0
~9.0.More simple preparation method can be used at this time: being added at one time whole water for injection, be placed in Agitation Tank, by place
Then 0.03%g/ml needle is added in side's amount investment sodium gluconate, sodium acetate, sodium chloride, potassium chloride and magnesium chloride, stirring and dissolving
With active carbon stirring and adsorbing 15min, successively with 0.45 μm of miillpore filter, 0.22 μm of micropore filtration filter, filling, 121 DEG C of hot pressing are gone out
Bacterium 12min.
More preferably, the sodium gluconate used, when being configured to 10mg/ml solution using water for injection,
PH value is 6.5~7.0, and the sodium acetate used, when being configured to 30mg/ml solution using water for injection, pH value
It is 8.3~8.8.More simple preparation method can be used at this time: being added at one time whole water for injection, be placed in Agitation Tank
In, 0.01% is then added by recipe quantity investment sodium gluconate, sodium acetate, sodium chloride, potassium chloride and magnesium chloride, stirring and dissolving
G/ml needle-use activated carbon stirring and adsorbing 15min, successively with 0.45 μm of miillpore filter, 0.22 μm of micropore filtration filter is filling, and 121 DEG C
Pressure sterilizing 12min.
In injection production process, activated carbon dosage is generally 0.1%g/ml~1%g/ml of solution weight, due to work
The absorption of property charcoal is to may cause the major reason of electrolyte losses in injection, in order to obtain electrolyte ingredient and vivo environment
More consistent Multiple electrolytes injection, present invention applicant attempt to reduce the usage amount of active carbon, and concentrated compounding method is respectively adopted
Or dilute method of matching prepares injection, and investigates the dosage pair of needle-use activated carbon in 0.01%g/ml~0.5g/ml range of water for injection
The influence of electrolyte losses, however the studies above discovery is minimum by needle-use activated carbon of the bacterial endotoxin control in critical field
Usage amount is the 0.08g/ml of water for injection, and the injection total chlorine amount prepared still only has 0.328%, and electrolyte ingredient still has
Greater loss.
In order to make up the electrolyte ingredient lost during the preparation process, present invention applicant is attempted again using Excess quantities
Preparation method to guarantee the electrolyte content of finished product, but finds that active carbon is to Cl in experimentation-、Na+、K+Deng suction
Attached ability has larger difference, leads to the loss amount of each ion component and non-uniform, therefore can not make up by Excess quantities
The ingredient of loss, can not be by Cl-、Na+、K+The concentration of ion controls in blood plasma normal range (NR).
During a large amount of experiment screening, present invention applicant's discovery, unexpectedly, when not using existing concentrated compounding method or dilute
Match liquid method with the traditional injection such as method, and match liquid technique with a kind of innovation: a step matches liquid method, i.e., by recipe quantity
Each group be placed in Agitation Tank, whole water for injection is added at one time, after stirring and dissolving, with or without the use of PH regulator
Adjusting makes solution pH value to 6.0~8.0, at this point, unexpectedly, without as concentrated compounding method or it is dilute with method must be added to
The needle-use activated carbon of 0.08g/ml or more, and it is simply added into 0.01g/ml~0.05%g/ml needle-use activated carbon, it is just fully able to reach
To the purpose of removal bacterial endotoxin, moreover, being surprisingly found that, the injection total chlorine amount of preparation can be controlled in 0.345% g/
Ml~0.365%g/ml, i.e. electrolyte content are up to 95% g/ml or more of labelled amount unexpectedly, so that each ion component, especially
Cl-Loss is few, can guarantee that it is consistent with internal plasmatic environment to the greatest extent, and greatly improve the safety of product
Property.Also, this preparation method process is reduced, easy to operate, additionally it is possible to be effectively reduced error and be introduced the probability of impurity.
It is described to make solution pH value be preferably 6.5~7.5 with or without the use of the adjusting of PH regulator, closer to human plasma PH
Environment.
When adjusting pH value using PH regulator, to avoid introducing other ions, the PH regulator be preferably hydrochloric acid or
Sodium hydroxide.
For buffer salt to sodium gluconate and sodium acetate, since the process route of its production is different, quality control is different,
And the difference with water quality when being configured to solution, the sodium gluconate and vinegar of different manufacturers and same producer's different batches
Sour sodium, the pH value of solution usually has biggish fluctuation, therefore the national drug standards are to sodium gluconate and sodium acetate solution
PH value define more wide in range range: national drug standards YBH13422006 regulation, raw materials of glucose acid sodium are matched with water
When 10mg/ml solution is made, pH value should be between 6.0~7.5, national drug standards WS-10001-(HD-0584)-
2002 regulations, when raw material sodium acetate is configured to 30mg/ml solution with water, pH value should be between 7.5~9.2, however, this hair
Bright applicant is in further research process, very accidental discovery, only when screening suitable raw material, i.e. gluconic acid
Sodium is using water for injection rather than general purified water is configured to 10mg/ml solution, and when its pH value is between 6.3~7.2, together
When, sodium acetate is using water for injection rather than general purified water is configured to 30mg/ml solution, and its pH value is at 8.0~9.0,
With the solution that prescription component and water for injection are directly prepared, pH value can be naturally fallen in 6.0~8.0 ranges unexpectedly, therefore
Without adjusting pH value in preparation process, and the production of general injection, batch output counted in face of several tons, PH adjusting often need
Spend 0.5~1.5 hour, the not only very complicated time-consuming of process, but also increase injection exposure duration and device contacts it is several
Rate causes injection to be easy the pollution by environment and instrument, and the present invention is due to having used special detection method, i.e., using injection
The solution for generally configuring with water rather than with water sodium gluconate and sodium acetate, in numerous different manufacturers and the above-mentioned raw materials of batch
Careful screening is carried out, and the raw material for meeting certain pH condition range is selected to prepare compound electrolyte solution, thus in compound electricity
The pH value for adjusting solution is avoided in the production process of electrolyte solution, simplifies production process, and thus bring another excellent
Gesture, it can just achieve the purpose that control bacterial endotoxin or heat source with the dosage of 0.03% g/ml active carbon, and further
Reduce the loss of electrolyte ingredient.
More preferably, when selection meets the buffering clock synchronization of the following conditions, i.e. sodium gluconate is prepared using water for injection
At 10mg/ml solution, and its pH value, between 6.5~7.0, sodium acetate is configured to 30mg/ml solution using water for injection, and
And its pH value is between 8.3~8.8, and with the solution that prescription component and water for injection are directly prepared, pH value naturally falls in 6.5~
7.5 range not only avoids the pH value for adjusting solution, and the present patent application people's will closer to human plasma pH value at this time
Other places it has also been found that, the usage amount of active carbon can be down to the i.e. controllable bacterial endotoxin of 0.01% g/ml or heat source, this may be with
Adsorption capacity of the active carbon under this pH condition injection that is related, and thus preparing, electrolyte content are up to labelled amount
98% g/ml or more, therefore the loss of electrolyte ingredient is in extremely low level.
The weight of each component in the prescription of Multiple electrolytes injection of the present invention, it is all give money as a gift it is pure after weight
Amount.
Comparative example
Comparative example 1
It is dilute to match method: the water for injection of total volume 80% being placed in Agitation Tank, puts into sodium gluconate, acetic acid by recipe quantity
Sodium, sodium chloride, potassium chloride and magnesium chloride, to being completely dissolved, benefit injects water to recipe quantity for stirring, adjusts PH to 7.5, is added
0.08%g/ml needle-use activated carbon, after stirring and adsorbing 20min, successively with 0.45 μm of miillpore filter, 0.22 μm of filtering with microporous membrane,
It is filling, 121 DEG C of pressure sterilizing 15min.
Comparative example 2
Multiple electrolytes injection is prepared according to prescription described in comparative example 1 and method, difference is making for needle-use activated carbon
Dosage is 0.07%g/ml.
Comparative example 3
According to prescription described in comparative example 1, injection is prepared with concentrated compounding method:
The water for injection of recipe quantity 50% is added in dense preparing tank, then by sodium chloride, sodium gluconate, sodium acetate, chlorination
Potassium and magnesium chloride are placed in Agitation Tank, stirring and dissolving, addition 0.08%g/ml needle-use activated carbon, after stirring and adsorbing 20min, 0.45
μm miillpore filter is filtered to dilute preparing tank, and benefit injects water to nearly full dose, pH to 7.5 is adjusted after mixing evenly, successively with 0.45 μ
M miillpore filter, 0.22 μm of filtering with microporous membrane, filling, 121 DEG C of pressure sterilizing 15min.
Comparative example 4
Multiple electrolytes injection is prepared according to prescription described in comparative example 3 and method, difference is making for needle-use activated carbon
Dosage is 0.07%g/ml.
Comparative example 5
Multiple electrolytes injection is prepared according to prescription described in CN101849961A embodiment 1 and method:
First the sodium gluconate of recipe quantity and sodium acetate are dissolved in the water for injection of total volume 800ml, add prescription
Sodium chloride, potassium chloride and the magnesium chloride of amount, which mix to, to be completely dissolved；Benefit injects water to 1000ml, uses 0.1mol/L
It is 7.4 that hydrochloric acid solution, which adjusts pH, heats medical fluid to 80 DEG C, adds the needle charcoal of 1g, stirring and adsorbing 30min, with 0.45 μ
M filtering with microporous membrane decarburization, then with 0.3 μm of miillpore filter refined filtration；Pack, sealing, 121 DEG C of pressure sterilizing 15min.
Comparative example 6
Multiple electrolytes injection is prepared according to prescription described in CN102935087B embodiment 5 and preparation method:
50L water for injection is added in dense preparing tank, weighs sodium chloride, sodium gluconate, sodium acetate, the potassium chloride of recipe quantity
It is set in dense preparing tank with magnesium chloride, puts into 0.1%g/mL needle-use activated carbon after dissolution to be mixed again, stir evenly, standing adsorption 15 is divided
Clock filters carbon removal into dilute preparing tank, and benefit injects water to nearly full dose, stirs evenly, and adjusts pH with 0.1mol/L sodium hydroxide
It is filling through 0.45 μm and 0.22 μm of filter refined filtration between 7.0~7.6,121 DEG C pressure sterilizing 15 minutes.
Comparative example 7
Be added at one time whole water for injection, be placed in Agitation Tank, by recipe quantity investment sodium gluconate, sodium acetate,
Sodium chloride, potassium chloride and magnesium chloride, stirring and dissolving make solution pH value to 7.0, are then added 0.05% using the adjusting of PH regulator
G/ml needle-use activated carbon stirring and adsorbing 15min, it is filling successively with 0.45 μm of miillpore filter, 0.22 μm of filtering with microporous membrane, 121
DEG C pressure sterilizing 15min.
Injection prepared by comparative example 1~7 is according to " Chinese Pharmacopoeia " (version in 2010) two III the first method of H of annex V inspections
Check weighing tenor, and provide that it must not cross 3/10000000ths containing heavy metal；It is attached according to " Chinese Pharmacopoeia " (version in 2010) two
It records the first method of IX H and checks visible foreign matters, and must not provide and detect visible foreign matters；According to " Chinese Pharmacopoeia " (version in 2010) two
One detection bacterium endotoxin of annex XI E method, and provide that the amount in every 1ml containing bacterial endotoxin must not exceed 0.5EU；According to
" Chinese Pharmacopoeia " (version in 2010) two annex IX second methods of C check particulate matter, and provide in every 1ml containing 10 μm and 10 μ
The particle of m or more must not cross 12, and the particle containing 25 μm and 25 μm or more must not cross 2.It the results are shown in Table 1.
1 comparative example 1-7 heavy metal of table, visible foreign matters, bacterial endotoxin and particulate determination result
The result shows that concentrated compounding method or dilute method of matching no matter is used to prepare Multiple electrolytes injection, it is required to that 0.08g/ is added
Ml or more needle-use activated carbon is adsorbed, could by bacterial endotoxin control in 0.5EU hereinafter, and prescription used in this application and
Method is only added 0.05%g/ml needle charcoal, the indexs such as heavy metal, visible foreign matters and bacterial endotoxin can be made to meet regulation,
And the result of insoluble granule is also superior to other methods.
Injection prepared by comparative example 1-7 is according to the national drug standards [WS1(X-225) -2003Z] the method into
The measurement of row total chlorine amount, sodium, potassium, magnesium, and be compared with plasmatic environment, it the results are shown in Table 2.
2 comparative example 1-7 electrolyte ingredient testing result of table
Note: according to the product design of Multiple electrolytes injection, the content of magnesium ion is slightly above the content of magnesium in blood plasma,
This primarily to effectively prevention of postoperative hypomagnesemia generation, caused by correcting because of magnesium deficiency the phenomenon that cardiac arrhythmia.
The result shows that with traditional concentrated compounding method or dilute matching method, or the compound electrolyte prepared in other patent document methods
Injection, electrolyte content loss greatly so that the ion concentration in injection, especially chlorinity, sodium content etc., with
Plasmatic environment difference is larger, is unfavorable for maintaining the balance of vivo environment, and comparative example 7 is prepared using the method for the invention,
Electrolyte content loss is minimum, and the chlorinity of the electrolyte injection of preparation, sodium content, potassium content are and in human normal blood plasma
Respectively at be grouped as more closely, therefore preparation method it is more reasonable, more meet Human Physiology demand, it is easier to keep needed by human body energy
The balance of amount.
Specific embodiment
Present invention will be further explained below with reference to specific examples.But these embodiments be only limitted to illustrate the present invention without
It is for limiting the scope of the invention.
Embodiment 1
Sodium gluconate is configured to 10mg/ml solution using water for injection, and measuring its pH value is 6.32, and sodium acetate uses note
It penetrates and is configured to 30mg/ml solution with water, measuring its pH value is 7.83.
Be added at one time whole water for injection, be placed in Agitation Tank, by recipe quantity investment sodium gluconate, sodium acetate,
Sodium chloride, potassium chloride and magnesium chloride, stirring and dissolving, measuring its pH value is 5.77, adjusts pH value to 6.0 with sodium hydroxide solution,
Then 0.05%g/ml needle-use activated carbon stirring and adsorbing 15min is added, successively with 0.45 μm of miillpore filter, 0.22 μm of miillpore filter
Filtering, filling, 121 DEG C of pressure sterilizing 12min.
Embodiment 2
Multiple electrolytes injection is prepared by prescription described in embodiment 1.
Wherein, sodium gluconate is configured to 10mg/ml solution using water for injection, and measuring its pH value is 7.55, sodium acetate
It is configured to 30mg/ml solution using water for injection, measuring its pH value is 8.25.
Be added at one time whole water for injection, be placed in Agitation Tank, by recipe quantity investment sodium gluconate, sodium acetate,
Sodium chloride, potassium chloride and magnesium chloride, stirring and dissolving, measuring its pH value is 8.32, adjusts pH value to 8.0, then with hydrochloric acid solution
0.05%g/ml needle-use activated carbon stirring and adsorbing 15min is added, successively with 0.45 μm of miillpore filter, 0.22 μm of filtering with microporous membrane,
It is filling, 121 DEG C of pressure sterilizing 12min.
Embodiment 3
Multiple electrolytes injection is prepared by prescription described in embodiment 1.
Wherein, sodium gluconate is configured to 10mg/ml solution using purified water, and measuring its pH value is 6.34, and sodium acetate makes
It is configured to 30mg/ml solution with purified water, measuring its pH value is 8.12.
Be added at one time whole water for injection, be placed in Agitation Tank, by recipe quantity investment sodium gluconate, sodium acetate,
Sodium chloride, potassium chloride and magnesium chloride, stirring and dissolving, measuring its pH value is 5.88, adjusts pH value to 6.0 with sodium hydroxide solution,
Then 0.05%g/ml needle-use activated carbon stirring and adsorbing 15min is added, successively with 0.45 μm of miillpore filter, 0.22 μm of miillpore filter
Filtering, filling, 121 DEG C of pressure sterilizing 12min.
Embodiment 4
Multiple electrolytes injection is prepared by prescription described in embodiment 1.
Wherein, sodium gluconate is configured to 10mg/ml solution using water for injection, and measuring its pH value is 6.35, sodium acetate
It is configured to 30mg/ml solution using water for injection, measuring its pH value is 8.06.
Be added at one time whole water for injection, be placed in Agitation Tank, by recipe quantity investment sodium gluconate, sodium acetate,
Sodium chloride, potassium chloride and magnesium chloride, stirring and dissolving, measuring its pH value is 6.14, and 0.03%g/ml needle-use activated carbon is then added and stirs
Absorption 15min is mixed, successively with 0.45 μm of miillpore filter, 0.22 μm of filtering with microporous membrane, filling, 121 DEG C of pressure sterilizing 12min.
Embodiment 5
Multiple electrolytes injection is prepared by prescription described in embodiment 1.
Wherein, sodium gluconate is configured to 10mg/ml solution using water for injection, and measuring its pH value is 7.18, sodium acetate
It is configured to 30mg/ml solution using water for injection, measuring its pH value is 8.96.
Be added at one time whole water for injection, be placed in Agitation Tank, by recipe quantity investment sodium gluconate, sodium acetate,
Sodium chloride, potassium chloride and magnesium chloride, stirring and dissolving, measuring its pH value is 7.83, and 0.03%g/ml needle-use activated carbon is then added and stirs
Absorption 15min is mixed, successively with 0.45 μm of miillpore filter, 0.22 μm of filtering with microporous membrane, filling, 121 DEG C of pressure sterilizing 12min.
Embodiment 6
Multiple electrolytes injection is prepared by prescription described in embodiment 1.
Wherein, sodium gluconate is configured to 10mg/ml solution using water for injection, and measuring its pH value is 6.54, sodium acetate
It is configured to 30mg/ml solution using water for injection, measuring its pH value is 8.37.
Be added at one time whole water for injection, be placed in Agitation Tank, by recipe quantity investment sodium gluconate, sodium acetate,
Sodium chloride, potassium chloride and magnesium chloride, stirring and dissolving, measuring its pH value is 6.58, and 0.01%g/ml needle-use activated carbon is then added and stirs
Absorption 15min is mixed, successively with 0.45 μm of miillpore filter, 0.22 μm of filtering with microporous membrane, filling, 121 DEG C of pressure sterilizing 12min.
Embodiment 7
Multiple electrolytes injection is prepared by prescription described in embodiment 1.
Wherein, sodium gluconate is configured to 10mg/ml solution using water for injection, and measuring its pH value is 6.93, sodium acetate
It is configured to 30mg/ml solution using water for injection, measuring its pH value is 8.78.
Be added at one time whole water for injection, be placed in Agitation Tank, by recipe quantity investment sodium gluconate, sodium acetate,
Sodium chloride, potassium chloride and magnesium chloride, stirring and dissolving, measuring its pH value is 7.47, and 0.01%g/ml needle-use activated carbon is then added and stirs
Absorption 15min is mixed, successively with 0.45 μm of miillpore filter, 0.22 μm of filtering with microporous membrane, filling, 121 DEG C of pressure sterilizing 12min.
PH value, heavy metal, visible foreign matters, bacterial endotoxin, particulate matter are carried out to the injection of embodiment 1-7 preparation
Inspection.It the results are shown in Table 3.
3 embodiment 1-7 heavy metal of table, visible foreign matters, bacterial endotoxin and particulate determination result
The measurement of total chlorine amount, sodium, potassium, magnesium is carried out to the injection of embodiment 1-7 preparation, and is compared with plasmatic environment
Compared with the results are shown in Table 4.
4 embodiment 1-6 electrolyte ingredient testing result of table
Claims (2)
1. a kind of injection pharmaceutical composition of compound electrolyte, medicinal ingredient composition is as follows:
Sodium chloride 5.26g
Sodium gluconate 5.02g
Sodium acetate 3.68g
Potassium chloride 0.37g
Magnesium chloride 0.30g
Water for injection 985ml,
When being characterized in that the sodium gluconate is configured to 10mg/ml solution using water for injection, pH value is 6.3~7.2, and
And the sodium acetate, when being configured to 30mg/ml solution using water for injection, pH value is 8.0~9.0, and the preparation method comprises the following steps:
It is added at one time whole water for injection, is placed in Agitation Tank, puts into sodium gluconate, sodium acetate, sodium chloride, chlorine by recipe quantity
Change potassium and magnesium chloride, stirring and dissolving, makes pH value of solution to 6.0~8.0,0.03%g/ml needle-use activated carbon stirring and adsorbing is then added
15min, successively with 0.45 μm of miillpore filter, 0.22 μm of filtering with microporous membrane, filling, 121 DEG C of pressure sterilizing 12min.
2. a kind of injection pharmaceutical composition of compound electrolyte, medicinal ingredient composition is as follows:
Sodium chloride 5.26g
Sodium gluconate 5.02g
Sodium acetate 3.68g
Potassium chloride 0.37g
Magnesium chloride 0.30g
Water for injection 985ml,
It is characterized in that pH value is 6.5~7.0 when the sodium gluconate is configured to 10mg/ml solution using water for injection,
And when the sodium acetate is configured to 30mg/ml solution using water for injection, pH value is 8.3~8.8, and preparation method
Are as follows: it is added at one time whole water for injection, is placed in Agitation Tank, puts into sodium gluconate, sodium acetate, chlorination by recipe quantity
Sodium, potassium chloride and magnesium chloride, stirring and dissolving make pH value of solution to 6.0~8.0, the stirring of 0.01%g/ml needle-use activated carbon are then added
15min is adsorbed, successively with 0.45 μm of miillpore filter, 0.22 μm of filtering with microporous membrane, filling, 121 DEG C of pressure sterilizing 12min.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1732975A (en) * | 2005-08-08 | 2006-02-15 | 陈旭良 | Prescription of compound electrolyte drug for injection and method for preparing the same |
| CN102935087A (en) * | 2012-11-22 | 2013-02-20 | 北京金康驰医药投资有限公司 | Compound electrolyte injection composition and preparation method thereof |
| CN103211774A (en) * | 2013-04-26 | 2013-07-24 | 成都苑东药业有限公司 | Gabexate mesylate composition for injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1732975A (en) * | 2005-08-08 | 2006-02-15 | 陈旭良 | Prescription of compound electrolyte drug for injection and method for preparing the same |
| CN102935087A (en) * | 2012-11-22 | 2013-02-20 | 北京金康驰医药投资有限公司 | Compound electrolyte injection composition and preparation method thereof |
| CN103211774A (en) * | 2013-04-26 | 2013-07-24 | 成都苑东药业有限公司 | Gabexate mesylate composition for injection and preparation method thereof |
Non-Patent Citations (1)
| Title |
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| 活性炭去除注射液中热原的工艺条件考察;范能全;《中国药师》;20121231;第15卷(第9期);第1301-1303页 |
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